Related Experiment Video
Updated: Mar 29, 2026
Bioluminescence Imaging of an Immunocompetent Animal Model for Glioblastoma
Published on: January 15, 2016
Oncolytic Virus VV-GMCSF-Lact and Human GM-CSF Against GL261 Glioma in Immunocompetent Mice
Alisa B Ageenko1,2, Natalia S Vasileva1,2, Anna S Chesnokova1
1Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Lavrentyev Avenue 8, Novosibirsk 630090, Russia.
Abstract:
Background/Objectives: Oncolytic viruses are an immunotherapeutic approach that can modulate the tumor microenvironment (TME), transforming immunologically 'cold' tumors into 'hot' ones. Insertion of genes encoding immunomodulatory proteins can further enhance antitumor immune responses. In this study, we compared the antitumor and immunomodulatory effects of the double recombinant vaccinia virus VV-GMCSF-Lact, which carries the human GM-CSF gene, with those of recombinant human GM-CSF (rhGM-CSF) in an immunocompetent murine GL261 glioma model. Methods: The study was conducted using a subcutaneous GL261 glioma model in immunocompetent C57BL/6 mice, comparing intratumoral VV-GMCSF-Lact and rhGM-CSF treatments with evaluation of immune cell populations by flow cytometry, tumor morphology by H&E staining, and tumor transcriptome profiles by RNA sequencing. Results: Flow cytometry showed that VV-GMCSF-Lact reduced the number of immunosuppressive cells in the TME of subcutaneously transplanted gliomas, targeting different components of the TME depending on animal sex. The immunotherapeutic effects of rhGM-CSF were less pronounced and primarily affected peripheral immune cells. Histological analysis revealed a decrease in mitotic figures in tumors from female mice after viral therapy. Transcriptome profiling of GL261 tumors demonstrated divergent gene expression patterns and cellular compositions between treatment groups. VV-GMCSF-Lact treatment was associated with a decreased proportion of malignant GL261 cells and CD8+ T lymphocytes, while rhGM-CSF treatment increased proportions of MDSCs, macrophages, NK cells, and tumor-associated neutrophils. Conclusions: Taken together, our data demonstrate that VV-GMCSF-Lact induces antitumor immune responses in murine GL261 glioma in vivo and modulates the tumor microenvironment more effectively than rhGM-CSF alone, supporting its potential for developing new strategies for glioma treatment.
Insights
A novel oncolytic virus, VV-GMCSF-Lact, effectively combats glioma by reprogramming the tumor microenvironment (TME). This virus shows superior antitumor and immunomodulatory effects compared to recombinant human GM-CSF (rhGM-CSF) in preclinical models.
Area of Science:
- Immunotherapy
- Virology
- Oncology
Background:
- Oncolytic viruses modulate the tumor microenvironment (TME), converting 'cold' tumors to 'hot' ones.
- Gene insertion of immunomodulatory proteins can enhance antitumor immunity.
- VV-GMCSF-Lact is a double recombinant vaccinia virus carrying the human granulocyte-macrophage colony-stimulating factor (GM-CSF) gene.
Purpose of the Study:
- To compare the antitumor and immunomodulatory effects of VV-GMCSF-Lact and recombinant human GM-CSF (rhGM-CSF).
- To evaluate these treatments in an immunocompetent murine GL261 glioma model.
Main Methods:
- Subcutaneous GL261 glioma model in C57BL/6 mice.
- Intratumoral administration of VV-GMCSF-Lact and rhGM-CSF.
- Analysis of immune cell populations (flow cytometry), tumor morphology (H&E staining), and transcriptome profiles (RNA sequencing).
Main Results:
- VV-GMCSF-Lact reduced immunosuppressive cells in the TME, with sex-dependent effects.
- rhGM-CSF had less pronounced effects, primarily impacting peripheral immune cells.
- VV-GMCSF-Lact treatment decreased malignant cells and CD8+ T lymphocytes, while rhGM-CSF increased myeloid-derived suppressor cells (MDSCs), macrophages, NK cells, and neutrophils.
Conclusions:
- VV-GMCSF-Lact induces robust antitumor immune responses in vivo.
- VV-GMCSF-Lact demonstrates superior TME modulation compared to rhGM-CSF alone.
- VV-GMCSF-Lact holds promise for novel glioma treatment strategies.
